WO1999020602A1

WO1999020602A1 - Method for producing aryl thiols by hydrogenating diaryldisulphides

Info

Publication number: WO1999020602A1
Application number: PCT/EP1998/006450
Authority: WO
Inventors: Friedrich-Wilhelm Ullrich; Helmut Fiege
Original assignee: Bayer Aktiengesellschaft
Priority date: 1997-10-22
Filing date: 1998-10-12
Publication date: 1999-04-29
Also published as: IL135114A0; US6500988B1; EP1027331A1; DE59805923D1; DE19746512A1; CN1277602A; JP2001520218A; EP1027331B1; ATE225769T1; AU1227799A

Abstract

The invention relates to a particularly advantageous method for producing aryl thiols through the catalytic hydrogenation of diaryldisulphides. According to the invention, the hydrogenation is carried out in a basic alcoholic medium.

Description

Process for the preparation of aryl mercaptans by hydrogenation of diaryl disulfides

The present invention relates to a particularly advantageous process for the preparation of aryl mercaptans by hydrogenation of diarylsulfides.

Aryl mercaptans are important intermediates for the production of pharmaceutical and agrochemical active substances (see e.g. EP-A 100 172, BE-A 887 423, US-A 3 912 757 and WO 96/25936).

A useful method for the production of aryl mercaptans consists in the reaction sequence of the reduction of aryl sulfochlorides with sodium sulfite to aryl sulfinic acid salts, further reduction with sulfurous acid to the diaryl disulfide and finally cleavage of the disulfide with sodium borohydride (DE-A 44 20 777). The cleavage of the disulfide with sodium borohydride is unsatisfactory here, although it is good

Yield proceeds, but with the sodium borohydride requires a reagent that is difficult to produce and therefore expensive.

Catalytic hydrogenative cleavages of diaryl disulfides have also been described, but they always run at high temperatures and pressures or require other disadvantageous measures. Thus, according to J. Org. Chem. 24, 1598 (1959), the reaction is carried out in toluene with a MoS ι ~ alumina catalyst at 140 ° C and 124 bar. DE-A 17 68 421 describes this hydrogenation with palladium contacts and Raney cobalt at 160 to 200 ° C. and 150 bar. According to JP-OS 60/199 871, the hydrogenation is carried out with Raney nickel in a heterogeneous solvent system which consists of two phases, namely an aqueous / alkaline and a water-insoluble organic phase.

If one proceeds to lower pressures and lower temperatures with these processes, the conversion is incomplete (see comparative examples

1 and 2). A process has now been found for the preparation of aryl mercaptans by catalytic hydrogenation of diaryl disulfides, which is characterized in that the hydrogenation is carried out in a basic alcoholic medium.

For example, aryl mercaptans can be obtained by the process according to the invention

Formula (I)

in the

R and R 'independently of one another each represent hydrogen, C _j -CG-alkyl, Ci-Cg-alkoxy or halogen,

produce from the corresponding diaryl disulfides of the formula (II)

in the

R and R 'have the meaning given for formula (I).

In formulas (I) and (II), R and R 'independently of one another are preferably hydrogen, methyl, ethyl, methoxy, ethoxy, fluorine or chlorine. R and R 'are particularly preferably hydrogen. The diaryl disulfides required as the starting product, in particular those of the formula (II), are accessible in various ways, for example according to DE-A 44 20 777. A method of particular interest here is one in which S- (4-biphenyl) sulfinic acid is used or their salts are reacted with an aqueous bisulfite solution at pH values from 2 to 7, so that the corresponding S- (4-biphenyl) thiosulfuric acids or their salts are obtained and these are heated in the presence of a strong aqueous acid. This process is detailed in one other patent application, which was filed simultaneously by the same applicant

As a solvent for the formation of the alcoholic required according to the invention

Medium are suitable, for example, aliphatic C 1 -C ₅ -alcohols, which can be straight-chain or branched. These can be primary, secondary or tertiary alcohols. Preferred are methanol, ethanol and isopropanol. The alcoholic medium can optionally also contain water, for example up to 20% by weight, preferably up to 10% by weight. For example, it is not necessary to use the diaryl disulfide in dried form. It can just as well be used in the form of the water-moist product obtained during its production. Mixtures of various alcohols can also be used as the alcoholic medium

Based on 1 mole of diaryl disulfide, for example, 200 to 10,000 ml of alcohol can be used

This amount is preferably 500 to 5000 ml

Alkali metal hydroxides, alkali metal carbonates or alkali metal alcoholates, in particular alkali-C 1 -C ₄ -alkyl alcoholates or corresponding alkaline earth metal compounds, for example alkali metal hydroxides, or corresponding alkaline earth metal compounds, are preferred as agents for producing a basic character in the alcoholic medium. Alkali metal hydroxides, in particular sodium and potassium hydroxide, are preferred

Based on 1 mol of diaryl disulfide, for example 0.5 to 5 equivalents of base can be used. This amount is preferably from 1.5 to 2.5 equivalents

Suitable catalysts for the hydrogenation according to the invention are, for example, metals from subgroup 8 of the PSE, in particular nickel and palladium of this type Metals can be used as such or as metal compounds. Metals or metal compounds can optionally be arranged on support materials such as activated carbon, aluminum oxide, alkaline earth carbonate or alkaline earth metal sulfate. The catalysts can be doped with further metals or metal compounds, for example those from subgroup 4 or 8 of the PSE. They can also in

The form of skeletal catalysts is present, for example in the Raney form. Preferred catalysts are palladium-on-carbon, palladium black, Raney nickel and Raney nickel doped with cobalt and / or iron. Raney nickel is particularly preferred

The catalytic hydrogenation according to the invention can, for example, at temperatures from 20 to

200 ° C. and pressures up to 50 bar are preferred. Temperatures from 40 to 150 ° C. and pressures up to 25 bar are preferred, in particular temperatures from 60 to 120 ° C. and pressures up to 15 bar

The reaction mixture present after the hydrogenation according to the invention can be worked up, for example, by cooling it, for example to from 20 to 65 ° C., and separating the catalyst, for example by filtration, and then the alcoholic solution of the aryl mercaptan prepared with acid and optionally water added and the then precipitating product is filtered off and dried

With the process according to the invention, aryl mercaptans, in particular diaryl mercaptans of the formula (I), can be obtained in good yields and purities

The method according to the invention has surprising advantages. It does not require any reagents that are difficult to produce. It can be carried out at lower temperatures and in particular at lower pressures than other methods, which means less expenditure on equipment and handling. Finally, it surprisingly avoids a complicated procedure with two liquid phases present side by side is in particular the fact that from Houben-Weyl, Methods of Organic Chemistry, Volume IX, S 77 (1955) in a basic medium

Disproportionation of disulfides to sulfinates and thiols is known. This undesirable reaction has hitherto been achieved by using water-immiscible tries to suppress solvents. Surprisingly, it has been shown that this is not necessary.

Examples

example 1

In a 0.3 1 stainless steel autoclave, 0.1 mol of bis (4-diphenyl) disulfide in one

Solution of 8 g of sodium hydroxide suspended in 220 g of ethanol and mixed with 1 g of Raney nickel. The mixture was hydrogenated at 80 ° C. with 10 bar hydrogen. After the hydrogen uptake had ended, the mixture was cooled and let down. After the catalyst had been filtered off at 60 ° C., the mixture was diluted with 150 ml of water and a pH of 1 was established with 20 ml of aqueous hydrochloric acid (37% by weight). The precipitated product was suctioned off and washed with water. After drying, 35.1 g of 4-mercaptodiphenyl with a content of 95.7% by weight were obtained. This corresponds to a yield of 90.2% of theory

Comparative Example 1

The hydrogenation was carried out as in Example 1, but without the addition of sodium hydroxide. No hydrogen was taken up. When the reaction mixture was worked up, only the feed was recovered.

Comparative Example 2 (analogous to JP-OS 60/199 871)

38.4 g of bis (4-diphenyl) disulfide were suspended in a two-phase system consisting of 100 ml of toluene and a solution of 8 g of sodium hydroxide in 150 ml of water. 1 g of Raney nickel were added and the mixture was hydrogenated at 80 ° C. and 10 bar. After 4

Hours of hydrogen absorption stopped. You cooled down and relaxed the approach.

In addition to the catalyst, the reaction mixture also contained unreacted bis (4-diphenyl) disulfide as a solid. Bis- (4-diphenyl) disulfide was also found in the toluene phase after concentration. The water phase was with

37% by weight aqueous hydrochloric acid acidified, the precipitated product is suctioned off and washed with 100 ml of water. After drying, 21.4 g of 4-mercapodiphenyl with a content of 93.6% by weight were obtained. This corresponds to a yield of 53.8% of theory

Example 2

The hydrogenation was carried out as in Example 1, but methanol was used as the solvent instead of ethanol. 37.1 g of 4-mercapodiphenyl with a content of 97.1% by weight were obtained. This corresponded to a yield of 96.7% of theory

Example 3

The hydrogenation was carried out as in Example 1, but isopropanol was used instead of ethanol as the solvent. 31.8 g of 4-mercapodiphenyl with a content of 81.7% by weight were obtained. This corresponded to a yield of 69.8% of theory

Example 4

189 g of bis (4-diphenyl) disulfide was prepared as described in Example 5, but used in the form of the moist filter cake (276 g) in the hydrogenation. For this purpose, the moist filter cake was slurried with 800 g of ethanol, 44 g of sodium hydroxide and 5.5 g of Raney nickel were added. The mixture was heated in an autoclave to 80 ° C and pressurized 10 bar of hydrogen. The hydrogen uptake ended after 4 hours. The mixture was cooled and let down. After filtering off the catalyst at 60 ° C., the filtrate was acidified with 840 ml of 5.4% by weight aqueous hydrochloric acid. The product failed. It was filtered off, washed with 250 ml of water and dried. 178.8 g of a white powder with a melting point of 110 to 112 ° C. were obtained. The 4-mercaptodiphenyl content was included

91.8% by weight (determined iodometrically). This results in a yield of 80.1% of theory based on diphenyl-4-sulfochloride originally used. Example 5 (Preparation of bis- (4-diphenyl) disulfide - not according to the invention)

400 ml of 39% by weight aqueous bisulfite liquor and 550 ml of water were initially charged with 125 ml of aqueous sodium hydroxide solution (45% by weight) and 2.2 g of triethylbenzylammonium chloride were added. The mixture was heated to 60 ° C. In the course of an hour, 289.5 g of diphenyl-4-sulfochloride (96% by weight) were introduced and at the same time the pH of the reaction mixture was kept at 8 by metering in 45% by weight aqueous sodium hydroxide solution, also during the three hours After stirring, the pH was kept constant by metering in sodium hydroxide solution.

The reaction mixture was then mixed in a 3 1 enamel autoclave with 80 ml of sulfur dioxide and heated to 130 ° C. for 3 hours. The batch was stirred for 6 hours at 130 ° C. and a pressure of 4.4 to 6.9 bar. Then it was cooled to room temperature and relaxed. The suspension obtained was suction filtered. The filter cake was dried. 237.4 g of solid with a bis- (4-diphenyl) disulfide content of 78.3% were obtained. This corresponds to a yield of 91.2% of theory

Claims

claims

1. A process for the preparation of aryl mercaptans by catalytic hydrogenation of diarylsulfides, characterized in that the hydrogenation is carried out in a basic alcoholic medium.

2. The method according to claim 1, characterized in that aryl mercaptans of the formula (I)

in the

R and R 'independently of one another each represent hydrogen, C _j -CG alkyl, C i -Cg- alkoxy or halogen,

from the corresponding diaryl disulfides of formula (II)

in the

R and R 'have the meaning given for formula (I).

3. Process according to Claims 1 and 2, characterized in that aliphatic C ₅ -C ₅ alcohols are used as the solvent for forming the alcoholic medium.

4. The method according to claims 1 to 3, characterized in that the alcoholic medium contains up to 20 wt .-% water.

5. Process according to Claims 1 to 4, characterized in that alkali metal hydroxides, alkali metal carbonates or alkali metal alcoholates or corresponding agents are used as agents for producing a basic character in the alcoholic medium

Uses alkaline earth compounds.

6. Process according to Claims 1 to 5, characterized in that 0.5 to 5 equivalents of base are used per 1 mol of diaryl disulfide.

7. Process according to Claims 1 to 6, characterized in that metals from subgroup 8 of the PSE are used as catalysts.

8. The method according to claims 1 to 7, characterized in that one carries out the catalytic hydrogenation at temperatures from 20 to 200 ° C and pressures up to 50 bar.

9. The method according to claims 1 to 8, characterized in that one carries out the catalytic hydrogenation at 40 to 150 ° C and pressures up to 25 bar.

10. The method according to claims 1 to 9, characterized in that the reaction mixture present after carrying out the catalytic hydrogenation is worked up by cooling it, separating the catalyst, adding the then present alcoholic solution of the aryl mercaptan produced with acid and then filtering off the precipitated product and dries.